Amsacrine hydrochloride - CAS 54301-15-4
Catalog number: 54301-15-4
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C21H20ClN3O3S
Molecular Weight:
429.92
COA:
Inquire
Targets:
Topoisomerase
Description:
Amsacrine hydrochloride is an antineoplastic agent which can intercalate into the DNA of tumor cells. It also expresses topoisomerase inhibitor activity, specifically inhibiting topoisomerase II.
Purity:
>98%
Synonyms:
AMSA hydrochloride; m-AMSA hydrochloride; CI-880 hydrochloride; SN-11841 hydrochloride; acridinyl anisidide hydrochloride
MSDS:
Inquire
InChIKey:
WDISRLXRMMTXEV-UHFFFAOYSA-N
InChI:
InChI=1S/C21H19N3O3S.ClH/c1-27-20-13-14(24-28(2,25)26)11-12-19(20)23-21-15-7-3-5-9-17(15)22-18-10-6-4-8-16(18)21;/h3-13,24H,1-2H3,(H,22,23);1H
Canonical SMILES:
COC1=C(C=CC(=C1)NS(=O)(=O)C)NC2=C3C=CC=CC3=NC4=CC=CC=C42.Cl
1.Cellular responses to methyl-N-[4-9-acridinylamino)-2-methoxyphenyl] carbamate hydrochloride, an analogue of amsacrine active against non-proliferating cells.
Moreland N1, Finlay GJ, Dragunow M, Holdaway KM, Baguley BC. Eur J Cancer. 1997 Sep;33(10):1668-76.
The acridine derivative m-AMCA (methyl-N-[4-(9-acridinylamino)-2-methoxyphenyl]carbamate hydrochloride), a carbamate analogue of the topoisomerase II poison amsacrine, is distinguished by its high cytotoxicity against non-cycling tumour cells. We compared the response of cultured Lewis lung carcinoma cells to m-AMCA, amsacrine and the topoisomerase I poison camptothecin. The DNA polymerase inhibitor aphidicolin reversed the cytotoxicity of camptothecin fully, that of amsacrine partially, and that of m-AMCA minimally. The ability of m-AMCA to induce the enzyme poly(ADP-ribose)polymerase (PARP) was markedly lower than that of camptothecin or amsacrine. Cell cycle responses to m-AMCA and amsacrine were similar, with slowing of progress through S-phase and arrest in G2-phase. These cell cycle changes were also observed when plateau phase cultures were exposed to drug for 1 h, washed free of drug and cultured in fresh medium, with m-AMCA having a more pronounced effect than amsacrine and camptothecin having no effect.
2.Mutation E522K in human DNA topoisomerase IIbeta confers resistance to methyl N-(4'-(9-acridinylamino)-phenyl)carbamate hydrochloride and methyl N-(4'-(9-acridinylamino)-3-methoxy-phenyl) methane sulfonamide but hypersensitivity to etoposide.
Leontiou C1, Lakey JH, Austin CA. Mol Pharmacol. 2004 Sep;66(3):430-9.
Human cells express two isoforms of topoisomerase II, alpha and beta, that are both targeted by anticancer drugs. To investigate acridine resistance mediated by topoisomerase IIbeta, we used a forced molecular evolution approach. A library of mutated topoisomerase IIbeta cDNAs was generated by hydroxylamine mutagenesis and was transformed into the yeast JN394 top2-4. Methyl N-(4'-(9-acridinylamino)-phenyl)carbamate hydrochloride (AMCA) selection identified a resistant transformant able to grow in media containing 76 microg/ml AMCA. Topoisomerase IIbeta with a glutamic acid-to-lysine substitution at position 522 was responsible for the approximately 10-fold resistance to AMCA. The transformant was cross-resistant to methyl N-(4'-(9-acridinylamino)-3-methoxy-phenyl) methane sulfonamide (mAMSA) and mAMCA but hypersensitive to etoposide and ellipticine. In vitro, the betaE522K protein was unable to support acridine-stimulated DNA cleavage, suggesting that resistance to these acridines is caused by reduced drug-stimulated DNA cleavage.
3.A carbamate analogue of amsacrine with activity against non-cycling cells stimulates topoisomerase II cleavage at DNA sites distinct from those of amsacrine.
Baguley BC1, Leteurtre F, Riou JF, Finlay GJ, Pommier Y. Eur J Cancer. 1997 Feb;33(2):272-9.
AMCA (methyl N-[4-(9-acridinylamino)-2-methoxyphenyl]carbamate hydrochloride), an amsacrine analogue containing a methylcarbamate rather than a methylsulphonamide side chain, contrasts with amsacrine, doxorubicin and etoposide in its relatively high cytotoxicity against non-cycling tumour cells. AMCA bound DNA more tightly than amsacrine, but the DNA base selectivity of binding, as measured by ethidium displacement from poly[dA-dT].[dA-dT] and poly[dG-dC].[dG-dC], was unchanged. AMCA-induced topoisomerase cleavage sites on pBR322, C-MYC and SV40 DNA were investigated using agarose or sequencing gels. DNA fragments were end-labelled, incubated with purified topoisomerase II from different mammalian sources and analysed after treatment with sodium dodecylsulphate/proteinase K. AMCA stimulated the cleavage activity of topoisomerase II, but the DNA sequence selectivity of cleavage was different from that of amsacrine and other topoisomerase inhibitors.
4.Amsacrine suppresses matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia cells.
Liu WH1, Chen YJ, Chien JH, Chang LS. J Cell Physiol. 2014 May;229(5):588-98. doi: 10.1002/jcp.24481.
This study explores the suppression mechanism of amsacrine (4-(9-Acridinylamino)-N-(methanesulfonyl)-m-anisidine hydrochloride) on matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in human leukemia cells. Amsacrine attenuated cell invasion with decreased MMP-2/MMP-9 protein expression and mRNA levels in U937, Jurkat, HL-60, K562, KU812, and MEG-01 cells. Moreover, amsacrine reduced both MMP-2/MMP-9 promoter luciferase activity and MMP-2/MMP-9 mRNA stability in leukemia cells. Studies on amsacrine-treated U937 cells revealed that amsacrine-elicited ROS generation induced JNK and p38 MAPK activation but reduced the phospho-ERK level. Amsacrine-induced ERK inactivation and p38 MAPK/JNK activation were demonstrated to suppress MMP-2/MMP-9 promoter luciferase activity and promote MMP-2/MMP-9 mRNA decay, respectively. p38 MAPK/JNK activation led to up-regulation of protein phosphatase 2A catalytic subunit α (PP2Acα) in amsacrine-treated U937 cells.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related Topoisomerase Products


CAS 33419-42-0 Etoposide

Etoposide
(CAS: 33419-42-0)

Etoposide is a semisynthetic derivative of podophyllotoxin, which inhibits DNA synthesis via topoisomerase II inhibition activity.

ABT-719
(CAS: 162829-90-5)

ABT-719, a fluoroquinolone derivative, has been found to be a DNA topoisomerase inhibitor that was once developed in antibacterial studies.

CAS 174634-09-4 TAS-103

TAS-103
(CAS: 174634-09-4)

TAS-103, also known as BMS-247615, is a quinoline derivative that displays antitumor activity in murine and human tumor models. TAS-103 has been reported to be ...

Tilfrinib
(CAS: 1600515-49-8)

Tilfrinib, a pyridoindol derivative, has been found to be a breast tumor kinase (Brk) inhibitor that could probably restrain the proliferation of breast cancer ...

CAS 78186-34-2 Bisantrene

Bisantrene
(CAS: 78186-34-2)

Bisantrene is an anthracenyl bishydrazone used as a particular anticancer drug. Bisantrene can lead to inhibition of DNA replicantion and DNA-protein crosslinki...

CAS 86639-52-3 SN-38

SN-38
(CAS: 86639-52-3)

SN-38 is the active metabolite of irinotecan. In vitro cytotoxicity assays show that the potency of SN-38 relative to irinotecan varies from 2- to 2000-fold. SN...

CAS 97682-44-5 Irinotecan

Irinotecan
(CAS: 97682-44-5)

Irinotecan is a topoisomerase I inhibitor for LoVo cells and HT-29 cells with IC50 of 15.8 μM and 5.17 μM, respectively.

CAS 29767-20-2 Teniposide

Teniposide
(CAS: 29767-20-2)

Teniposide is a chemotherapeutic medication mainly used in the treatment of childhood acute lymphocytic leukemia (ALL).It is in a class of drugs known as podoph...

Chemical Structure

CAS 54301-15-4 Amsacrine hydrochloride

Quick Inquiry

Verification code

Featured Items